【摘要】 目的：分析冠心苏合丸溶胀微针的治疗效果，研究其治疗心肌缺血的作用机制。方法：通过BATMAN-TCM数据库获得冠心苏合丸活性成分并分析其对应靶点；在CTD、Gencards、OMIM、PharmGKB、DiGSeE和DisGeNET六个数据库中获得疾病相关靶点；经STRING数据库构建PPI网络及拓扑分析找到关键靶点，再进行基因本体（GO）功能分析与京都基因与基因组百科全书（KEGG）通路富集分析。通过HE染色和ELISA实验验证微针穴位贴敷对大鼠心肌缺血的影响。通过荧光定量PCR和WB实验验证微针穴位贴敷作用于心肌缺血的分子机制。结果：共筛选出72种有效成分及593个治疗心肌缺血的可能靶点。富集分析结果提示其主要涉及的信号通路包括c AMP信号通路、cGMP-PKG信号通路及钙信号通路等。实验结果表明冠心苏合丸溶胀微针穴位贴敷以及阳性药物处理对心肌缺血大鼠具有显著保护作用，可改善心肌组织病理状态。微针穴位贴敷通过上调PRKACA和CREB的表达水平，促进抗凋亡因子Bcl-2的表达并抑制促凋亡因子Bax的产生，从而发挥心肌缺血保护作用。这一作用机制可能与其调控cAMP信号通路密切相关。结论：网络药理学分析结果显示，冠心苏合丸作用于心肌缺血与cAMP信号通路密切相关。冠心苏合丸溶胀微针穴位贴敷可通过调节凋亡相关因子Bcl-2与Bax的表达比例，从而参与调控cAMP信号通路，最终实现对心肌缺血病理状态的改善作用。更多还原

【Abstract】 Objective: To systematically analyze the therapeutic efficacy of the swelling microneedle formulation of Guanxin Suhe Pill and elucidate its underlying mechanism in treating myocardial ischemia. Methods:The active components of Guanxin Suhe Pill were identified using the BATMAN-TCM database, and their corresponding targets were analyzed. Disease-related targets were retrieved from six databases: CTD, Gencards,OMIM, PharmGKB, DiGSeE, and Dis Ge NET. A protein-protein interaction(PPI) network was constructed via the STRING database, followed by topological analysis to identify key targets. Subsequently, Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed. The effects of the swelling microneedle acupoint application of Guanxin Suhe Pill on myocardial ischemia in rats were validated through hematoxylin-eosin(HE) staining and enzyme-linked immunosorbent assay(ELISA). The molecular mechanisms underlying the protective effects of the swelling microneedle acupoint application on myocardial ischemia were further confirmed using quantitative real-time polymerase chain reaction(qRT-PCR) and Western blot(WB) analyses. Results: A total of 72 active components and 593 potential targets associated with the treatment of myocardial ischemia were identified. Enrichment analysis revealed that the primary pathways involved were the cAMP signaling pathway, cGMP-PKG signaling pathway,calcium signaling pathway, among others. Experimental findings demonstrated that both the swelling microneedle formulation of Guanxin Suhe Pill and positive drug treatments significantly protected against myocardial ischemia in rats, improving the pathological condition of myocardial tissue. The protective effects of the swelling microneedle acupoint application were attributed to the upregulation of PRKACA and CREB expression levels, promotion of anti-apoptotic factor Bcl-2 expression, and inhibition of pro-apoptotic factor Bax production. This mechanism is likely closely associated with the regulation of the cAMP signaling pathway. Conclusion: The results of network pharmacological analysis indicate that Guanxin Suhe Pill’s effect on myocardial ischemia is closely associated with the cAMP signaling pathway. The application of swelling microneedle acupoint application of Guanxin Suhe Pill can regulate the expression ratio of apoptosis-related factors Bcl-2 and Bax, thereby participating in the modulation of the cAMP signaling pathway and ultimately achieving an improvement in the pathological state of myocardial ischemia.更多还原